Linggui Zhugan Decoction: A Potential Weight Reduction Solution via Gut Microbiota and Cinnamic Acid Metabolites

Linggui Zhugan Decoction (LGZGD) has demonstrated promising potential in the treatment of obesity, prompting further investigation. In a study involving sixty-nine obese patients who received LGZGD for two months, changes in body composition, gut microbiota, and plasma metabolomics were assessed. An animal experiment with ob/ob mice assessed LGZGD and antibiotics’ effects on body weight, fat mass, gut microbiota, and metabolomics. Clinical results showed LGZGD reduced body weight, fat, and waist-to-hip ratio, improved gut microbiota diversity favoring beneficial strains, and revealed Cinnamic acid presence in non-targeted plasma metabolomics. In obese mice, LGZGD effectively reduced body weight and fat mass, with this effect attenuated in microbiota-depletedmice. The treatment also influenced gut microbiome composition, aligning it more closely with that of normal mice. Non-targeted metabolomics analysis identified various metabolites in stool and plasma, including Cinnamic acid. In vitro experiments demonstrated that Cinnamic acid, devoid of toxicity, inhibited lipid synthesis and improved lipid metabolism in adipocytes. The immunofluorescence demonstrated Cinnamic acid activated the expression of Uncoupling protein 1 in differentiated adipocytes in a dose-dependent way. This study suggests that LGZGD’s weight-reduction effects are mediated through interactions with gut microbiota and its metabolites. Activating the browning of white adipocytes maybe the underlying mechanism.